(a) Field of the Invention
This invention relates to a coated aspirin tablet and its preparation. In particular, the invention relates to an aqueous spray-coating method of preparing an easily-swallowed, powder-free and gastric-disintegrable aspirin tablet thinly-coated with hydroxypropyl methylcellulose and the tablet produced thereby.
(b) Description of the Prior Art
Aspirin tablets historically have been difficult to film coat as they are friable, dusty, and easily dissolved by water and organic solvents. Aspirin itself is readily decomposed by moisture and heat. Successful films have been applied from organic solvents using air as well as airless spray processing primarily because of the low flash points and rapid evaporation of the solvents involved.
S. F. Jeffries U.S. Pat. No. 3,149,040, issued Sept. 15, 1964, shows thin film coating of tablets with a particular mixture of cellulose acetate phthalate, a polyoxyethylene derivative of polypropylene glycol and plasticizer, said mixture applied in a non-aqueous system. No such coated aspirin tablets are shown. Moreover, nonaqueous coating systems are now undesirable from an environmental standpoint.
J. L. Anderson et al. U.S. Pat. No. 3,341,416, issued Sept. 12, 1967, discloses the encapsulation of minute particles of aspirin in ethylcellulose, using a cyclohexane solution of the latter. The encapsulated particles are said to provide "a minimum amount of release" of aspirin "in the stomach" and a continuing release of aspirin "slowly all along the extent of the intestinal tract."
E. H. Gans et al. U.S. Pat. No. 3,388,041, issued June 11, 1968, teaches the preparation of a high dosage sustained release tablet containing aspirin which comprises granulating aspirin with a solution of a mixture of hydroxypropyl methylcellulose and ethylcellulose in a volatile organic solvent, drying the coated granules and compressing the granules into sustained released tablets, which slowly release aspirin "for a period of up to twelve hours". Gans et al. also discloses a preferred two-ply laminate tablet using two different aspirin granulation compositions, namely: (1) said granulated aspirin coated with the combination of hydroxypropyl methylcellulose and ethylcellulose to provide slow release of aspirin over a period of up to twelve hours; and, (2) a composition of an uncoated mixture of aspirin and starch to provide rapid release of aspirin.
H. R. Hawthorn Australian Pat. No. 477,515, published July 17, 1975, shows the application to aspirin tablets of an enteric coating comprising a mixture of hydroxypropyl methylcellulose phthalate and ethyl cellulose using a solution of the coating materials in a mixture of methylene dichloride and alcohol, thereby providing a tablet with a coating of sufficient thickness to pass unchanged through the stomach.
R. E. Singiser U.S. Pat. No. 3,256,111, issued June 14, 1966, shows a method of applying a protective glossy coating to previously coated and dried tablets by spray-coating hydroxypropyl methylcellulose in a non-aqueous solvent. Although Singiser appreciated the advantages of hydroxypropyl methylcellulose being soluble in water as well as in organic solvents, he used only its non-aqueous solutions in his spray-coating method. The only previously coated tablets gloss-coated by Singiser are vitamin tablets.
Y. Tuji U.S. Pat. No. 3,477,864, issued Nov. 11, 1969, shows a process for coating tablets, etc., with a moisture-preventing and thermostable film, said process which comprises: (a) preparing a coating composition by dissolving hydroxypropyl methylcellulose in a mixture of at least one low boiling aliphatic halide and at least one other selected low boiling organic solvent and adding to the solution one of three prescribed sealing agents; (b) spraying the composition onto the tablets, etc., being rolled in a usual coating pan; (c) drying the coated tablets, etc.; and (d) repeating the spraying and drying. The only tablets shown contain sodium chloride, sucrose, corn starch and magnesium stearate. The solvent system used to prepare the coating composition is environmentally undesirable and the disintegration times of the coated tablets actually are greater than that of the uncoated tablets.
An article entitled "Coating tablets with water based solutions" [Manufacturing Chemist & Aerosol News, p. 31, January 1976], which is based on trials by Manesty Machines Ltd. Liverpool, England, recommends very low viscosity grades (between 6 and 15 cps) of hydroxypropyl methylcellulose, preferably with a water-soluble plasticizer, and slowly rotating pan speeds, e.g., as low as 21/2 rpm. Problems of aqueous spray-coating of tablets are discussed. There is no mention of any particular pharmaceutical ingredients in the uncoated tablets. This publication states that "the plasticisers that can be used is limited to water solubles"; however, it states that "glycerol and propylene glycol were not particularly successful". Although this publication generally states "that even water-sensitive tablets can be successfully coated without the penetration of water affecting the material", it is believed that such a general statement would not lead one skilled in the art of pharmaceutical production to applicants' process described below. It is well known that manufacturers of aspirin and aspirin tablets, from start to finish, scrupulously avoid all exposure of this analgesic or its tablets to water. In fact, manufacturers of aspirin tablets control the humidity of processing rooms to prevent decomposition of the aspirin and its tablets. Accordingly, it is believed to be non-obvious to purposely spray an aqueous coating solution with concurrent heating onto uncoated aspirin tablets as unexpectedly done successfully by applicants in their process described hereinbelow.
S. Ohno et al. U.S. Pat. No. 4,017,647, issued Apr. 12, 1977, relates to a "Method for Providing Enteric Coatings on Solid Dosage Forms". Example 3 of this patent shows aqueous spray-coating of aspirin tablets with hydroxypropyl methylcellulose phthalate, treating the coated tablets with 3 N hydrochloric acid at 20.degree. C., washing the acid-treated product with water and drying the washed enteric-coated tablets. These tablets, unlike applicants' tablets discussed below, "remained unchanged in the simulated gastric fluid and were completely disintegrated in the simulated intestinal fluid within a period of from 4 minutes and 50 seconds to 5 minutes and 30 seconds". In contrast, applicants' coated tablets disintegrate in simulated gastric fluid in less than one minute.
P. R. Sheth U.S. Pat. No. 4,167,558, issued Sept. 11, 1979, relates to a sustained release aspirin tablet containing from about 20% by weight to about 75% by weight of one or a mixture of hydrocolloids, e.g., hydroxypropyl methylcellulose, said tablet which provides, upon contact with gastric fluid, a water impermeable barrier on its surface and which acquires and maintains a bulk density of less than one thereby being buoyant in said fluid and remaining buoyant in the gastric fluid of the stomach until substantially all of the aspirin contained therein is released over a prolonged period.